Biology subjects

Stacey, J. A.

Publications and source records attributed to Stacey, J. A..

3 recordsLinked to original sources

bioRxiv2024

Perinatal serotonin signalling dynamically influences the development of cortical GABAergic circuits with consequences for lifelong sensory encoding

Serotonin plays a prominent role in neurodevelopment, regulating processes from cell division to synaptic connectivity1,2. Clinical studies suggest that alterations in serotonin signalling such as genetic polymorphisms3-5 or antidepressant exposure during pregnancy6,7 are risk factors for neurodevelopmental disorders. However, an understanding of how dysfunctional neuromodulation alters systems level activity over neocortical development is lacking. Here, we use a longitudinal imaging approach to investigate how genetics, pharmacology, and aversive experience disrupt state-dependent serotonin signalling with pathological consequences for sensory processing. We find that all three factors lead to increased neocortical serotonin levels during the initial postnatal period. Genetic deletion of the serotonin transporter or antidepressant dosing results in a switch from hypo- to hyper-cortical activity that arises as a consequence of altered cortical GABAergic microcircuitry. However, the trajectories of these manipulations differ with postnatal exposure to antidepressants having effects on adult sensory encoding. The latter is not seen in the genetic model despite a similar early phenotype, and a distinct influence of maternal genotype on the development of supragranular layers. These results reveal the dynamics and critical nature of serotonin signalling during perinatal life; pharmacological targeting of which can have profound life-long consequences for cognitive development of the offspring.

neuroscience↗

bioRxiv2023

GABAergic circuits reflect different requirements for emergent perception in postnatal mouse neocortex

Information transfer in the mammalian cerebral cortex is dependent on locally-projecting GABAergic interneuron circuits that are widely assumed to be uniform across neocortical areas. We demonstrate that this does not hold true during the highly dynamic period of postnatal life prior to the onset of active sensory exploration. During this time, a subset of interneuron defined by expression of the neuropeptide somatostatin differentially contribute to sensory-evoked activity in primary somatosensory and visual cortices. This functional divergence between the two areas is explained by differences in the composition of somatostatin interneuron subtypes and the transient circuits formed by these cells; the somatosensory circuit representing an adaptation to control early neonatal touch information. Understanding such area-dependent differences will promote our endeavours to understand the aetiology of developmental psychiatric disorders. Summary SentenceCortical circuits are adapted to the local information processing demands of the developing brain

neuroscience↗

bioRxiv2023

Uncovering bacterial hosts of class 1 integrons in an urban coastal aquatic environment with a single-cell fusion-PCR technology

Horizontal gene transfer (HGT) is a key driver of bacterial evolution via transmission of genetic materials across taxa. Class 1 integrons are genetic elements that correlate strongly with anthropogenic pollution and contribute to the spread of antimicrobial resistance (AMR) genes via HGT. Despite their significance to human health, there is a shortage of robust, culture-free surveillance technologies for identifying uncultivated environmental taxa that harbour class 1 integrons. We developed a modified version of epicPCR (emulsion, paired isolation and concatenation polymerase chain reaction) that links class 1 integrons amplified from single bacterial cells to taxonomic markers from the same cells in emulsified aqueous droplets. Using this single-cell genomic approach and Nanopore sequencing, we successfully assigned class 1 integron gene cassette arrays containing mostly AMR genes to their hosts in coastal water samples that were affected by pollution. Our work presents the first application of epicPCR for targeting variable, multi-gene loci of interest. We also identified the Rhizobacter genus as novel hosts of class 1 integrons. These findings establish epicPCR as a powerful tool for linking taxa to class 1 integrons in environmental bacterial communities and offer the potential to direct mitigation efforts towards hotspots of class 1 integron-mediated dissemination of AMR. SynopsisWe present a novel single-cell genomic surveillance technology for identifying environmental bacterial hosts of a class of mobile genetic elements that are linked to anthropogenic pollution and contribute to the dissemination of antimicrobial resistance.

microbiology↗